The program is concerned with animal model development and specifically those which have a direct application to human disease. The major emphasis is on those systems which define the immune system. The ultimate goal is developing a mouse system which is deficient in T-lymphocytes, B-lymphocytes, macrophages and natural killer cell (NK) activity. In turn, each one of these defects may be reintroduced into the immunodeficient mouse to study the role of these components of the immune system, either singly or combination, in bringing about immune responses to neoplasms, parasites and bacterial infections. In addition, a program is underway to also explore the role of gene Avy, which has a major physiological effect in the expression of neoplasms in combination with the above immunologically defined mice.